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Polymorphisms of methylenetetrahydrofolate reductase (MTHFR) and methionine synthase (MTR) are related to cognitive dysfunction and mental disability. These genes, along with folate and vitamin B 12 levels, are regulators of one-carbon metabolism, which synthesizes S-adenosylmethionine (SAM) as a methyl donor for arsenic methylation. The aim of this study was to explore whether polymorphisms of MTHFR and MTR influence arsenic methylation capacity and plasma folate and vitamin B 12 levels and if these influences cause developmental delay in preschool children. A total of 178 children with developmental delay and 88 without developmental delay were recruited from August 2010 to March 2014. A high-performance liquid chromatography-hydride generator and atomic absorption spectrometer were used to determine urinary arsenic species. Plasma folate and vitamin B 12 concentrations were measured by SimulTRAC-SNB radioassay. Polymorphisms of MTHFR C677T, MTHFR A1298C, and MTR A2756G were examined by polymerase chain reaction and restriction fragment length variation. The results show that MTHFR C677T C/T and T/T genotypes had a lower risk of developmental delay than the C/C genotype (odds ratio [OR] = 0.47; 95% confidence interval, 0.26-0.85). Subjects with the MTHFR C677T C/C genotype had significantly lower plasma folate and vitamin B 12 levels than those with the MTHFR C677T C/T and T/T genotype. The MTHFR C677T C/C genotype combined with high total urinary arsenic and poor arsenic methylation capacity indices significantly increased the OR of developmental delay in a dose-response manner. This is the first study to show the combined effect of MTHFR C677T genotype and poor arsenic methylation capacity on developmental delay.

Developmental delay has been associated with inefficient arsenic methylation capacity in preschool children. Folate and vitamin B12 are important nutrients that produce s-adenosylmethionine during single-carbon metabolism and provide methyl groups for arsenic methylation. The aim of the present study was to explore whether plasma folate and vitamin B12 levels influence arsenic methylation capacity and in turn are related to developmental delay in preschool children. A case-control study was conducted in 178 children with developmental delay and 88 normal children, who were recruited from Shin Kong Wu Ho-Su Memorial Teaching Hospital from August 2010 to March 2014. Arsenite (As III ), arsenate (As V ), monomethylarsonic acid (MMA V ), and dimethylarsinic acid (DMA V ) in the urine was determined by high-performance liquid chromatography-linked hydride generator and atomic absorption spectrometry. Plasma folate and vitamin B12 levels were measured using a SimulTRAC-SNB radioassay. The results show that the combination of high plasma folate and high vitamin B12 levels were correlated with efficient arsenic methylation capacity (low MMA V  %, low InAs %, and high DMA V  %). High MMA V  % significantly increased and high DMA V  % and secondary methylation index decreased the odds ratio (OR) of developmental delay in a dose-dependent manner in both low plasma folate and low vitamin B12 (low/low) groups; the multivariate OR and 95% confidence interval were 5.01 (0.83-30.06), 0.21 (0.04-1.23), and 0.20 (0.03-1.20), respectively. This is the first study to show that the combination of high plasma folate and high vitamin B12 levels increases arsenic methylation capacity and indirectly decreases the OR of developmental delay in preschool children.

This study investigated the effects of a short-term family-centered workshop for children with developmental delays.This study was conducted in a rehabilitation outpatient clinic of a teaching hospital. We recruited 30 children with developmental delays and their parents as the study group and 57 age- and sex-matched children with typical development and their parents as the control group. The workshop was conducted for the children with developmental delays and their parents in the form of one 2-hour session per week for 6 weeks by health and education professionals by using a family-centered multidisciplinary approach. The Mandarin-Chinese Communicative Developmental Inventory and Peabody Developmental Motor Scales-Second Edition were used to assess the communication and motor skills of the children with developmental delays. The parent form of the Pediatric Outcomes Data Collection Instrument, Child Health Questionnaire, Pediatric Quality of Life (PedsQL) Inventory, and PedsQL Family Impact Module were administered to the parents of both groups.On study commencement, no significant differences were noted in functional performance and family impact between the children with developmental delays and those without delays. The children with developmental delays had lower health and health-related quality of life (HRQOL) scores than the children with typical development. Following the workshop, the study group exhibited significant improvements in physical health (94.2 vs 80.2, effect size: 1.00, P = .026), global function (94.8 vs 78.7, effect size: 0.88, P = .006), impact of the child's health on parental HRQOL (85.0 vs 70.4, effect size: 0.81, P = .043), and parental HRQOL (81.3 vs 65.0, effect size: 0.81, P = .015). No significant differences were recorded in function, health, HRQOL, or family impact between the children with developmental delays and those with typical development after 6 weeks.The multidisciplinary short-term family-centered workshop for children with developmental delays improved the children's physical health and global functional skills, and it reduced the impact of the child's health on parental HRQOL while also improving parental HRQOL.

Inefficient arsenic methylation capacity has been associated with developmental delay in children. The present study was designed to explore whether polymorphisms and haplotypes of arsenic methyltransferase (AS3MT), glutathione-S-transferase omegas (GSTOs), and purine nucleoside phosphorylase (PNP) affect arsenic methylation capacity and developmental delay. A case-control study was conducted from August 2010 to March 2014. All participants were recruited from the Shin Kong Wu Ho-Su Memorial Teaching Hospital. In total, 179 children with developmental delay and 88 children without delay were recruited. Urinary arsenic species, including arsenite (As III ), arsenate (As V ), monomethylarsonic acid (MMA V ), and dimethylarsinic acid (DMA V ) were measured using a high-performance liquid chromatography-linked hydride generator and atomic absorption spectrometry. The polymorphisms of AS3MT, GSTO, and PNP were performed using the Sequenom MassARRAY platform with iPLEX Gold chemistry. Polymorphisms of AS3MT genes were found to affect susceptibility to developmental delay in children, but GSTO and PNP polymorphisms were not. Participants with AS3MT rs3740392 A/G+G/G genotype, compared with AS3MT rs3740392 A/A genotype, had a significantly lower secondary methylation index. This may result in an increased OR for developmental delay. Participants with the AS3MT high-risk haplotype had a significantly higher OR than those with AS3MT low-risk haplotypes [OR and 95% CI, 1.59 (1.08-2.34)]. This is the first study to show a joint dose-response effect of this AS3MT high-risk haplotype and inefficient arsenic methylation capacity on developmental delay. Our data provide evidence that AS3MT genes are related to developmental delay and may partially influence arsenic methylation capacity., (Copyright © 2017 Elsevier Inc. All rights reserved.)

The aim of this study was to evaluate the association of blood lead, mercury, and cadmium concentrations with developmental delays and to explore the association of these concentrations with the health status of children. This study recruited 89 children with developmental delays and 89 age- and sex-matched children with typical development. Their health status was evaluated using the Pediatric Quality of Life (PedsQL) Inventory for health-related quality of life (HRQOL) and the Pediatric Outcomes Data Collection Instrument for function. Family function was also evaluated. Blood lead, mercury, and cadmium concentrations were measured using inductively coupled mass spectrometry. The children with developmental delays had a considerably poorer HRQOL, lower functional performance and family function, and a higher blood lead concentration than those with typical development. The blood lead concentration had a significantly positive association with developmental delays [odds ratio (OR) = 1.54, p < 0.01] in a dose-response manner, and it negatively correlated with PedsQL scores (regression coefficient: -0. 47 to -0.53, p < 0.05) in all the children studied. The higher blood cadmium concentration showed a significantly positive association with developmental delays (OR = 2.24, for >1.0 μg/L vs. <0.6 μg/L, p < 0.05). The blood mercury concentration was not associated with developmental delays and health status.

This case-control study identified the association between the arsenic methylation capacity and developmental delays and explored the association of this capacity with the health status of children. We recruited 120 children with developmental delays and 120 age- and sex-matched children without developmental delays. The health status of the children was assessed using the Pediatric Quality of Life Inventory (PedsQL) and Pediatric Outcomes Data Collection Instrument (PODCI). The arsenic methylation capacity was determined by the percentages of inorganic arsenic (InAs%), monomethylarsonic acid (MMA V %), and dimethylarsinic acid (DMA V %) through liquid chromatography and hydride generation atomic absorption spectrometry. Developmental delays were significantly positively associated with the total urinary arsenic concentration, InAs%, and MMA V %, and was significantly negatively associated with DMA V % in a dose-dependent manner. MMA V % was negatively associated with the health-related quality of life (HRQOL; -1.19 to -1.46, P < 0.01) and functional performance (-0.82 to -1.14, P < 0.01), whereas DMA V % was positively associated with HRQOL (0.33-0.35, P < 0.05) and functional performance (0.21-0.39, P < 0.01-0.05) in all children and in those with developmental delays. The arsenic methylation capacity is dose-dependently associated with developmental delays and with the health status of children, particularly those with developmental delays.

We investigated the clinical efficacy on family functioning and parental satisfaction of a short-term family-centered workshop for children with developmental delays.A total of 32 children with developmental delays and their parents participated in 2-hour weekly group therapy sessions over 6 weeks. The workshop was conducted by rehabilitation professionals and teachers using a family-centered multidisciplinary approach. Both before and after the 6-week workshop, the parents were administered the Pediatric Quality of Life Inventory (PedsQL) Family Impact Module, the PedsQL Healthcare Satisfaction Module, the Hospital Anxiety and Depression Scale, and the World Health Organization Quality of Life brief assessment instrument. Overall satisfaction with the workshop was also evaluated.Significant improvements were noted in physical aspect (P = 0.03), communication (P = 0.002), and daily activities (P = 0.04) in the PedsQL Family Impact Module, and in communication (P = 0.03) and technical skills (P = 0.05) in the PedsQL Healthcare Satisfaction Module. Overall satisfaction with the workshop was rated as very high. There was no significant effect on psychological distress or quality of life.Short-term family-centered workshops for children with developmental delays improved family functioning and the parental perception of satisfaction, including health care satisfaction.

Unlabelled: This prospective, randomized controlled study investigated the effects of short-term interactive video game playing among children with developmental delays participating in traditional rehabilitation treatment at a rehabilitation clinic. One hundred and one boys and 46 girls with a mean age of 5.8 years (range: 3 to 12 years) were enrolled in this study. All patients were confirmed to suffer from developmental delays, and were participating in traditional rehabilitation treatment. Children participated in two periods of 4 weeks each, group A being offered intervention of eight 30-minute sessions of interactive video games in the first period, and group B in the second, in addition to the traditional rehabilitation treatment. The physical, psychosocial, and total health of the children was periodically assessed using the parent-reported Pediatric Quality of Life Inventory-Generic Core Scales (PedsQL); and the children's upper extremity and physical function, transfer and basic mobility, sports and physical functioning, and global functioning were assessed using the Pediatric Outcomes Data Collection Instrument. Parental impact was evaluated using the PedsQL-Family Impact Module for family function, PedsQL-Health Satisfaction questionnaire for parents' satisfaction with their children's care and World Health Organization-Quality of Life-Brief Version for quality of life. Compared with the baseline, significant improvements of physical function were observed in both groups (5.6 ± 19.5, p = 0.013; 4.7 ± 13.8, p = 0.009) during the intervention periods. No significant improvement of psychosocial health, functional performance, or family impact was observed in children with developmental delays. Short-term interactive video game play in conjunction with traditional rehabilitation treatment improved the physical health of children with developmental delays., Trial Registration: ClinicalTrials.gov NCT02184715.

Environmental exposure to lead or mercury can cause neurodevelopmental damage. Arsenic is another neurotoxicant that can affect intellectual function in children. This study was designed to explore the difference of arsenic methylation capacity indices between with and without developmental delay in preschool children. We also aimed to identify whether blood levels of lead or mercury modify the effect of arsenic methylation capacity indices. A cross sectional study was conducted from August 2010 to March 2012. All participants recruited from the Shin Kong Wu Ho-Su Memorial Teaching Hospital. In all, 63 children with developmental delay and 35 children without developmental delay were recruited. Urinary arsenic species, including arsenite (As(III)), arsenate (As(V)), monomethylarsonic acid (MMA(V)) and dimethylarsinic acid (DMA(V)) were measured with a high-performance liquid chromatography-linked hydride generator and atomic absorption spectrometry. Lead and mercury levels of red blood cells were measured by inductively coupled mass spectrometry. All participants underwent developmental assessments to confirm developmental delays, including evaluations of gross motor, fine motor, speech-language, cognition, social, and emotional domains. Urinary total arsenic and MMA(V) percentage were significantly positively associated and DMA(V) percentage was negatively associated with the risk of developmental delay in a dose-dependent manner after adjustment for blood lead or mercury levels and other risk factors. A multivariate regression analysis indicated that blood lead level and arsenic methylation capacity each independently contributed to the risk of developmental delay. This is the first study to show that arsenic methylation capacity is associated with developmental delay, even without obvious environmental arsenic exposure., (Copyright © 2014 Elsevier GmbH. All rights reserved.)

Objective: To examine the correlation of function, quality of life (QOL), and parental impact on developmental delayed children., Methods: Sixty parents of children with developmental delays (M:F = 36:24, mean age 4 years and 2 months) and 56 parents of age-sex matched typical development children were included. Pediatric Outcomes Data Collection Instrument and Child Health Questionnaire for children, World Health Organization-QOL, Impact on Family Scale, and Hospital Anxiety and Depression Scale for parents were assessed., Results: Functional performance was correlated with physical component of QOL in children (correlation coefficients: 0.7-0.9; p < 0.01), age of children (0.3-0.4; p < 0.05) and parents (0.3; p < 0.05), maternal employment (0.3-0.4; p < 0.05), parental QOL (0.3-0.4; p < 0.01), family impact (-0.3 to -0.5; p < 0.01), and parental emotion (-0.3 to -0.4; p < 0.05)., Conclusions: Children who exhibited higher levels of function had higher QOL, as did their parents, and less parental impact.

Aims: The study aims to evaluate the quality of life (QOL) and health of children with unclassified developmental delays and the impacts this had on the family., Methods: In total, 60 parents of pre-school children with unclassified developmental delays and 56 parents of age and gender-matched children with typical development were recruited. We administered the Pediatric Quality of Life Inventory (PedsQL)-Generic Core Scale and Pediatric Outcomes Data Collection Instrument to parents to evaluate the QOL and health status of their children. Parents were evaluated by World Health Organization-Quality of Life-Brief Version, PedsQL-Family Impact Module, Hospital Anxiety and Depression Scale, and PedsQL-Health satisfaction to assess the impacts of this situation on the family. Variables related to QOL and functions of children with unclassified developmental delays were analysed by stepwise regression analysis., Results: Comparing children with typical development, children with unclassified developmental delays had a significantly lower QOL (including both psychosocial and physical components) and health status. Their parents had a significantly lower QOL, family function and health satisfaction, and higher psychological distress than parents of children with typical development. Gross-motor delay impacts on QOL of these children (regression coefficient: -9.59, P < 0.05), global functioning is related to cognition delay (regression coefficient: -20.22, P < 0.01) and physical health of their parents (regression coefficient: 0.87, P < 0.01)., Conclusions: Children with unclassified developmental delays had lower QOL and health status, and their condition had greater impacts on the family than children with typical development. Gross motor and cognition development related to the QOL and global functioning in these children., (© 2013 The Authors. Journal of Paediatrics and Child Health © 2013 Paediatrics and Child Health Division (Royal Australasian College of Physicians).)